10.57647/jnsc.2026.1603.13

Engineering Gold Nanocluster/Polymer Hybrid Nanocarriers to Boost Doxorubicin Transport and Cellular Uptake in Gastric Cancer Cells

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  • Yong He*1,
  • Jinshi Chen1,
  • Cheng-San Wong2,
  1. R&D Department of 3D Printing, Department of Gastrointestinal Surgery, Digestive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China
  2. School of Medicine, Sun Yat-sen University, Shenzhen 518107, China

Received: 17-12-2025

Revised: 27-01-2026

Accepted: 12-02-2026

Published in Issue 30-06-2026

Copyright (c) 2026 Yong He, Jinshi Chen, Cheng-San Wong (Author)

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

How to Cite

He, Y., Chen, J., & Wong, C.-S. (2026). Engineering Gold Nanocluster/Polymer Hybrid Nanocarriers to Boost Doxorubicin Transport and Cellular Uptake in Gastric Cancer Cells. Journal of Nanostructure in Chemistry, 16(3 (June 2026). https://doi.org/10.57647/jnsc.2026.1603.13
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Abstract

A pH-responsive, fluorescence-traceable core–shell nanosystem was prepared by co-encapsulating bovine serum albumin–templated Au nanoclusters and doxorubicin within ionotropically crosslinked chitosan (TPP gelation) to enhance intracellular chemotherapy delivery. Formulation screening (CS:TPP 3:1–6:1) identified an optimal composition with a hydrodynamic diameter of 145 ± 5 nm, PDI 0.18, and a surface potential of +32.4 ± 1.2 mV; TEM resolved 2.1 ± 0.3 nm clusters and uniform spherical particles. The lyophilized carriers displayed mesoporosity (SBET 42.5 m2/g; pore volume 0.15 cm3/g; mean pore size 12.4 nm). High drug incorporation was achieved (encapsulation efficiency 82.3 ± 1.4%; loading capacity 12.6 ± 0.8%). Dialysis experiments revealed gated release, with ~22% (pH 7.4) versus ~65% (pH 5.0) at 24 h and ~35% versus ~88% at 72 h; acidic kinetics followed the Korsmeyer–Peppas model (R2 = 0.985; n = 0.65). Hemolysis remained 1.2% at 100 μg/mL and <3.0% at 1000 μg/mL, and blank carriers preserved >90% viability at 500 μg/mL. In MGC-803 and SGC-7901 cells, the formulation lowered 48 h IC50 from 1.85 ± 0.12 to 0.92 ± 0.08 μg/mL and from 2.10 ± 0.15 to 1.15 ± 0.10 μg/mL, respectively. Uptake quantification showed a 4 h mean fluorescence intensity of 717 a.u. versus 280 a.u. for free drug, and apoptosis increased to 59.0% (early apoptosis 35.6%) compared with 40.6% (22.1%) for free drug. Confocal imaging showed time-dependent cytoplasmic-to-nuclear redistribution with persistent cluster fluorescence, supporting tracking. Together, these results suggest that enhanced cell-surface association driven by the cationic shell, combined with endo/lysosomal acidification–triggered reler exposure while limiting premature leakage under physiological pH.

Keywords

  • Adsorptive endocytosis,
  • Flow cytometry,
  • Ionic gelation,
  • Mesoporous texture,
  • PH-gated diffusion
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